Jobs had right idea, say HK cancer experts

PUBLISHED : Sunday, 13 November, 2011, 12:00am
UPDATED : Sunday, 13 November, 2011, 12:00am


In life, Steve Jobs revolutionised the computing and media industries. Then, while dying from pancreatic cancer, he helped his doctors pioneer treatments that, only a few years ago, might have sounded like science fiction.

One key treatment used on Jobs, called molecular targeted therapy, is already under research in Hong Kong and will be available to hospital patients here early next year.

After his cancer diagnosis in 2004, Jobs first tried alternative medical approaches. But once he decided on mainstream cancer treatment, he pushed his doctors to experiment at the limits and frontiers of contemporary medical science.

He spent more than US$100,000 to have DNA sequencing performed both on his normal DNA and that of his tumours. Knowing the unique genetic and molecular signature of Jobs' tumours enabled his doctors to pick specific drugs that directly targeted the defective molecular pathways that caused his cancer cells to grow abnormally.

The goal was to change Jobs' pancreatic cancer from a killer into something manageable. His biographer, Walter Isaacson, wrote of a day soon when such cancers will 'be considered a manageable chronic disease, which could be kept at bay until the patient died of something else.'

In Hong Kong, the DNA technology for diagnosing disease and detecting mutating bacteria is already being used by researchers at the University of Hong Kong and Chinese University.

Dr Edmond Ma Shiu-kwan, director of clinical pathology and molecular pathology at the Hong Kong Sanatorium and Hospital, says the institution will start applying the new technology for testing cancer and inherited diseases in patients next year.

However its normal application will not involve Jobs' extreme example of sequencing someone's entire DNA, but only the tumour's genetic material, Ma says.

'Steve Jobs underwent the most comprehensive analysis, and we're not proposing to do the same thing ... bcause it's a Herculean task. It involves a lot of effort and huge expenses. Instead of doing the whole genome, we try to look at cancer-specific genes.'

Ma said conventional treatments cannot distinguish between normal cells and cancer cells. But by isolating the cancer cells, molecular targeted therapy 'lets doctors use drugs that are only detrimental to the cancer cells, and that by and large don't damage the body's normal cells.'

He added: 'The growth of a tumor is out of control, a mutation not subject to the body's normal regulation. If we can identify this mutation, we can use a tailor-made drug - an inhibitor. It's a small molecule inhibitor that will lead to cell death of the tumour.

'The tumour is relying on the mutation for its growth. It's like the tumour is addicted to this growth-enhancing signal, which also becomes its Achilles' heel: If we knock it down, there's very little... room for the tumour cell to escape.'

Many oncologists believe molecular therapy is the chemotherapy of the future. In the United States, the National Cancer Institute's molecular targets development programme (MTDP) is committed to identifying and evaluating molecular targets that may be candidates for drug development.

In Hong Kong, the universities are carrying out research into this molecular focus, although the government does not have a department dealing with it.

Researchers say the next stage of targeted therapies will focus on finding out which patients will respond to which particular targeted therapies - a process called the identification of 'sub-populations', stratified medicine or even personalised medicine. This may, for example, involve tailor-making drugs that target the unique genetic makeup of a patient.

In Jobs' case, the massive full-body gene sequencing and analyses work was done collaboratively by teams at Stanford, Johns Hopkins and the Broad Institute of MIT and Harvard. 'Thanks to some pioneering science, the team of doctors had been able to keep Jobs one step ahead of the cancer,' his biographer wrote.

'This approach ... was more effective than traditional chemotherapy, which attacks the process of division of all the body's cells, cancerous of not.

'This targeted therapy was not a silver bullet, but at times it seemed close to one: it allowed his doctors to look at a large number of drugs - common and uncommon, already available or only in development - to see which three of four might work best. Whenever his cancer mutated and repaved around one of these drugs, the doctors had another drug lined up to go next.'

If a person's tumour contains genetic mutations that can be targeted by specific drugs, doctors can use those drugs to save a patient's life.

Indeed, doctors and companies are already offer this service to patients, or plan to very soon. There are about 200 genes, they say, that can be targeted by specific drugs.

According to a local oncologist, it is not necessary to sequence a patient's whole genome to read these 200 genes, which make up less than 0.02 per cent of a person's total DNA. So the cost of performing this test now - about US$4,000 - is a fraction of what Jobs paid.

It's not known, however, whether these targeted therapies actually prolonged Jobs' life longer than standard chemotherapy would have, particularly because he underwent standard chemotherapy as well.

A host of celebrities, scientists and business titans have increasingly lined up for genome sequencing, which is becoming inexpensive enough that more and more ordinary people are having their DNA analysed, too. One scientist has estimated that about 5,000 people will be sequenced this year, and 30,000 next year.

They include hundreds of cancer patients around the world, although most are anonymous subjects in research studies.

Documents relating to those who have been sequenced almost always tell the same story: how the sequence has helped lead to a cure or better treatment.

For instance, sequencing revealed that a severely ill Wisconsin boy could be cured of his sickness by a bone marrow transplant.

But that is not how things played out for Jobs. He told Isaacson early this year, 'I'm either going to be one of the first to be able to outrun a cancer like this, or I'm going to be one of the last to die from it.'

Unfortunately, the cancer ultimately caught up with him by early 2008, and passed anything that even the most cutting-edge oncological medicine could throw at it.